Reflections From a Long Sunday at ASH – Part One

I started the day listening to oral presentations about a number of experimental therapies. No blockbuster news. But I would be glad to share my thoughts.

I’m not going to write about dosing data in any of these studies, even though dosing safety is the primary function of a Phase I/II study. The good thing about the Phase I/II designation: researchers are starting to get an idea if the therapy is going to work. Unfortunately, some of the data was incomplete and studies ongoing.

The first presentation I watched were results from a Phase I/II study featuring Daratumumab, a CD38 monoclonal antibody.

Like most immunotherapy agents, daratumumab’s safety profile looked good–very safe and few side effects. The trial had only been ongoing for eight weeks, so I’m not sure why data was being presented yet. Immunotherapy hype, I guess.

All of the studies I’m going to mention here were conducted using heavily pretreated patients. In this case, they had used an average of five or six prior therapies. Most of the 500 or so clinicians in the audience realize that this drug will probably never be used by itself. So to expect much while testing it as a stand-alone agent is a bit unrealistic. For example, another immunotherapy agent, elotuzumab, only works when combined with another novel therapy agent like Revlimid.

That said, there was some positive response after 8 weeks: 13% of the patients achieved a partial response (PR), 19% a marginal response (MR) and 16% of the test subjects were able to maintain stable disease. If my math is correct, that means almost one half responded. Let’s give this study and incomplete.

Next up: Final results of a Phase I/II trial featuring lenalidomide, thalidomide and dexamethasone. Let’s use trade names and call it Thalomid/Revlimid/dex.
This study was designed to try and see if adding Thalomid to the mix could help overcome Revlimid resistance.

I’m personally interested in this approach after hearing Dr. Orlowski at last year’s ASH rave about the positive response he had gotten while using this combination in patients that had become refractory (resistant) to Revlimid at M.D. Anderson Cancer Center in Houston.

Here, the overall response rate (OS) was 51%. Not bad! 13% reached a complete response (CR), BUT most patients were only pre-treated and refractory to one agent or another, meaning that some patients in the study had yet to become refractory to Revlimid. Why include them in the study? My guess is it was too difficult to find enough Revlimid resistant patients to participate. I understand, but it sort of waters things down, don’t you think?

Not surprisingly, patients that responded best lived the longest, On the grim side, those patients with stable disease–or worse–died on average in a 10 months.

It’s always hard to concentrate on the what the presenter is saying when I hear things like that. But fortunately, there is always something else to report on…

Like a single agent Phase I/II trial of dinaciclib (SCH727965), a novel CDK inhibitor. Please don’t ask me what a CDK inhibitor is. But I do know that this technology is brand new. Our docs are looking for a new class of drugs to break-through and join the IMiDs (Thalomid, Relvlimid and pomalidomide) and proteasome inhibitors (Velcade, Kyprolis, MLN-9708). At first glance, CDK inhibitors may not make the cut.

Of 27 patients in the study. 40% had high risk disease. 100% were heavily pre-treated.

The most common side effect included GI issues. GREAT! Not many side effects! While only 6 patients responded, the remaining majority did develop stable disease.

But this is where one needs to read between the lines. For example, one patient did show an amazing response, even after being treated with just about everything, from cytoxan to pomalidomide–and everything in-between.

Researchers are excited about the possibility of combining dinaciclib with proteasome inhibitor. And that’s my point. Sounds like this could end-up being a worthwhile assisting, combination therapy agent.

Remember, a therapy doesn’t need to be a “blockbuster” to be helpful someday. Combinations are where it’s at! And combining one of these new drugs with existing winners may hold the key to producing a long lasting, deep response in some patients. Create enough different combinations, match them up with the right patient–at the right dose–and BAM! We all start living longer. One step closer to what I call a “chronic cure.”

Let’s stop here for now. I’m off to the next meeting. I already have enough material for two week’s worth of posts–and today is by far the busiest myeloma related day at the conference.

So I will fill in the gaps as time goes on. This afternoon I will pass-along some more data, along with my feelings about if and how anything I am seeing here is going to help me and my fellow myeloma patients anytime soon. I think you will be pleasantly surprised! Let’s just say I’m cautiously optimistic.